FDA Grants Breakthrough Therapy Designation to ICT01 in Frontline AML

The FDA has granted breakthrough therapy designation to first-line IPN60340 (ICT01), a novel anti-BTN3A monoclonal antibody, in combination with venetoclax (Venclexta) and azacitidine as a treatment for unfit acute myeloid leukemia (AML), according to a news release from the developer, Ipsen.¹

Developers engineered ICT01 to recognize and eliminate tumor cells via γ9δ2 T cells, which play a role in the immunosurveillance of malignancy and infections. When binding to and altering the conformation of BTN3A, the novel agent selectively activates circulating γ9δ2 T cells into the tumor tissue, triggering a downstream immunological cascade through the secretion of proinflammatory cytokines that further boost an antitumor response.

“This breakthrough therapy designation recognizes both the urgent need for new treatment options for [patients] living with [AML] and the promising data seen so far in the development program for IPN60340,” Christelle Huguet, PhD, executive vice president and head of Research & Development at Ipsen, stated in the news release.¹ “We look forward to working closely with the FDA as we advance to the next stage of clinical development and continue to deliver medicines with the potential to be transformative to people living with cancer.”

Supporting data for the breakthrough designation came from the phase 1/2 EVICTION trial (NCT04243499), in which investigators evaluated ICT01 among patients with various advanced relapsed or refractory solid tumors or hematologic malignancies with no standard treatment options. Investigators presented updated findings from the AML cohort of the EVICTION trial at the 2025 American Society of Hematology Annual Meeting & Exposition (ASH).²

Among 38 patients who received a low dose of ICT01 and 16 who received a high dose of ICT01 in combination with venetoclax/azacitidine, a complete response (CR) occurred in 71% (95% CI, 54%-85%) and 44% (95% CI, 20%-70%), respectively. Additionally, among 11 and 9 patients from each dosing group with TP53 mutations, the respective CR rates were 55% (95% CI, 23%-83%) and 44% (95% CI, 14%-79%). Across different molecular subtypes of disease, investigators noted that responses rates were typically higher for patients who received the low dose of ICT01.

With a median follow-up of 10.8 months (95% CI, 8.9-12.8), the median duration of response (DOR) was not reached (NR) among patients who received the low dose of ICT01 and 9.3 months among those who received the high dose. Additionally, the median overall survival (OS) was NR (95% CI, 10.4-NR) and 10.9 months (95% CI, 1.7-NR) with each respective dose (HR, 0.5; 95% CI, 0.2-1.1; P = .07).

In the low-dose and high-dose groups, respectively, notable treatment-emergent adverse effects included febrile neutropenia (51% vs 50%), pneumonia (24% vs 25%), sepsis (27% vs 19%), and cytokine release syndrome (10% vs 13%). The hematological toxicities were expected based on prior reports of venetoclax/azacitidine-based regimens, and investigators noted a lower rate of grade 5 sepsis and pneumonia with the low dose of ICT01.

In cohort F of the EVICTION trial, patients 75 years and older with newly diagnosed AML or those considered unfit for intensive chemotherapy were randomly assigned to receive 75 mg of ICT01 via sustained γ9δ2 T-cell activation (n = 16) or a low dose of 10 mg via transient γ9δ2 T-cell activation (n = 19) plus venetoclax/azacitidine during the dose-finding portion of the trial. In the dose-expansion phase of the study, 22 patients received ICT01 at the lower dose of 10 mg.

The trial’s primary end point was CR rate based on ELN 2022 criteria. Key secondary end points included safety, the composite CR rate, DOR, and OS.

References

1. U.S. FDA grants Ipsen’s IPN60340 (ICT01) breakthrough therapy designation in first line unfit acute myeloid leukemia. News release. Ipsen. January 13, 2026. Accessed January 14, 2026. https://tinyurl.com/s3bd4xz2
2. Garciaz S, Dumas P-Y, Peterlin P, et al. γ9δ2 T-cell (γ9δ2TC) activation with ICT01 and azacitidine-venetoclax (Aza-Ven) induces high rates of remission and overall survival in patients with newly diagnosed (ND) acute myeloid leukemia (AML): results from the phase 1/2 study eviction. Blood. 2025;146(suppl 1):652. doi:10.1182/blood-2025-652